Search Results (157,297)

This review examines the feasibility of electrochemical synthesis of poly-L-arginine (PArg) using repetitive cyclic voltammetry in neutral aqueous phosphate-buffered saline. Previous studies on electrochemical deposition of PArg onto different carbonaceous electrode materials are discussed with respect to the already reported mechanistic models. Some controversial interpretations are of interest, predominantly the formation of peptide bonds during the electropolymerisation of L-arginine. Several alternative anodic pathways are considered via the possibilities and limitations of ways of attaching L-arginine molecules to the electrode surface. Furthermore, the role of oxygen-containing surface groups is discussed, as this aspect has been largely overlooked in the context of L-arginine deposition, despite the O-terminating character of the electrode surface and its effect on the reactivity of the nucleophilic guanidine group in L-arginine. Also, the application of extremely high potentials around +2 V vs. Ag/AgCl/3 mol L⁻¹ KCl is considered, as it can lead to the generation of reactive oxygen species that may interfere with or even govern the entire deposition process. Thus, the absence of such considerations may raise doubts about the peptide nature of the electrochemically assisted polymerisation of this basic amino acid. Finally, it seems that the identity of the electrochemically synthesised PArg does not correspond to that of this polymer prepared by conventional methods, such as solid-phase peptide synthesis, solution-phase synthesis, or N-carboxy-anhydride polymerisation, and therefore the whole process remains unproved. Full article

Piscine lactococcosis is an emerging bacterial disease that threatens freshwater and marine aquaculture in the Mediterranean region. This study characterized isolates of Lactococcus garvieae and Lactococcus petauri from farmed fish through molecular identification, genomic typing and antimicrobial susceptibility testing. A total of 39 bacterial strains were analyzed using species-specific real-time PCR assays, multilocus sequence typing and broth microdilution to determine minimum inhibitory concentrations. Results suggest a temporal shift in freshwater systems, where L. garvieae predominated in earlier isolates (mainly ST13, CC4), while L. petauri (ST14, CC14) appears as the dominant species in recent years. In marine fish, only L. garvieae was detected, mainly ST95 (CC95), a lineage previously reported in Europe. Molecular variability was found in both species with lineages capable of infecting livestock and humans. Amoxicillin displayed promising results; florfenicol showed moderate activity, while flumequine exhibited no inhibitory effect. Oxytetracycline and trimethoprim–sulfamethoxazole showed variable results requiring prudent use. These region-specific susceptibility profiles provide updated baseline data to guide empirical antimicrobial therapy while awaiting laboratory confirmation, highlighting the evolution of lactococcosis in aquaculture and emphasizing the need for molecular surveillance, antimicrobial stewardship, and vaccine updates within a One Health framework to mitigate impacts on Mediterranean aquaculture and public health. Full article

Obesity is closely linked to dyslipidemia, hepatic injury, and chronic inflammation through disturbances in the gut–liver axis. Here, we evaluated the anti-obesity effects of L. rhamnosus (Lacticaseibacillus rhamnosus) CU262 in a high-fat diet (HFD) mouse model and elucidated mechanisms using an integrated multi-omics strategy. Male C57BL/6 mice received CU262 during 12 weeks of HFD feeding. Phenotypes, serum/liver biochemistry, gut microbiota (16S rRNA sequencing), fecal short-chain fatty acids (SCFAs), and hepatic transcriptomes (RNA-seq) were assessed. CU262 significantly attenuated weight gain and adiposity; improved serum TC, TG, LDL-C and HDL-C; lowered ALT/AST and FFA; and mitigated oxidative stress and inflammatory imbalance (↓ IL-6/TNF-α, ↑ IL-10). CU262 restored alpha diversity, reduced the Firmicutes/Bacteroidetes ratio, enriched beneficial taxa (e.g., Akkermansia), and increased acetate and butyrate. Liver transcriptomics showed CU262 reversed HFD-induced activation of cholesterol/steroid biosynthesis and endoplasmic reticulum stress, with downregulation of key genes (Mvk, Mvd, Fdps, Nsdhl, and Dhcr7) and Pcsk9, yielding negative enrichment of steroid and terpenoid backbone pathways and enhancement of oxidative phosphorylation and glutathione metabolism. Correlation analyses linked Akkermansia and SCFAs with improved lipid/inflammatory indices and repression of cholesterol-synthetic and stress-response genes. These findings demonstrate that CU262 alleviates HFD-induced metabolic derangements via microbiota-SCFA-hepatic gene network reprogramming along the gut–liver axis, supporting its potential as a functional probiotic for obesity management. Full article

Immune checkpoint inhibitors (ICIs) for cancer therapy may induce immune-related adverse events including myocarditis, which occurs infrequently but carries a high mortality rate. Crocins are the active constituents derived from Crocus sativus L. (saffron), and have demonstrated various bioactivities including anti-tumor, anti-inflammation, antioxidation, anti-ischemia, anti-aging, and neuroprotective effects. This study established a subcutaneous xenotransplanted tumor model of human liver cancer in nude mice to better mimic ICI-related myocarditis. Animal experimental results revealed that crocins improved cardiac function, relieved myocardial damage and autoimmune response, and suppressed oxidative stress and inflammatory reaction. Quantitative proteomics and Western blotting verification confirmed that crocins ameliorated experimental ICI-related myocarditis by targeting the Hpx/Nrf2/HO-1 pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I–HO-1, crocin II–Hpx, and crocin III–Nrf2. These findings shed new light on the development of therapeutic strategies for treating ICI-related myocarditis and provided the fundamental basis for expanding the clinical application of crocins. Full article

Introduction: Immune evasion through inhibition of effector T cells is a key survival mechanism of lymphoma cells. We hypothesized that reinstating effector T cell activity through concurrent inhibition of the PD1/PD-L1 axis and of Treg activity will result in a synergistic anti-tumor effect with an acceptable toxicity profile. Methods: Phase I multi-institutional NCI-ETCTN trial aimed to evaluate the safety and tolerability of the combination of mogamulizumab and pembrolizumab in relapsed or refractory non-Hodgkin lymphoma. The study used a 3 + 3 design. Treatment consisted of mogamulizumab 1 mg/kg on days 1, 8, and 15 of cycle 1, followed by 1.5 mg/kg on day 1 of each subsequent 21-day cycle in combination with pembrolizumab 200 mg on day 1 of each cycle. A de-escalation level was defined as a 50% reduction in the dose of mogamulizumab (registered in clinicaltrials.gov NCT03309878). Results: The study was discontinued early, after treating seven patients (two angioimmunoblastic T cell lymphoma, four transformed follicular lymphoma, and one diffuse large B cell lymphoma of germinal center subtype) for concerns of futility and non-tolerability. Only two patients completed the first two cycles of treatment. Three patients presented with an early progression and three withdrew consent in the setting of general deterioration with clinically suspected progression. All six patients expired shortly after withdrawal from the study. The remaining patient experienced stress cardiomyopathy during the third cycle and was taken off the study. Discussion: In striking difference to the observation in solid malignancies, the combination of mogamulizumab with pembrolizumab was associated with low tolerability and suspected hyper-progression in patients with lymphoma. Full article

Azole selenoureas exhibit diverse biological functions. However, the synthesis and biological activity of benzothiazole and benzoxazole selenones remained unexplored. Herein, we report the base-catalyzed synthesis of N-difluoromethyl benzothiazole (or benzoxazole) selenone derivatives, which demonstrated significant antifungal efficacy against Rhizoctonia solani, Phytophthora infestans, Botrytis cinerea, and Fusarium oxysporum. Compound 3b exhibited exceptional antifungal activity against R. solani, with an EC₅₀ of 2.10 mg/L. Moreover, it substantially inhibited sclerotia germination (81.5% at 9 mg/L) and formation (79.3% at 9 mg/L), surpassing octhilinone. The protective effect on detached rice leaves and rice seedlings was found to be 43.4% and 85.2% at 100 mg/L, respectively, and 64.4% and 89.4% at 200 mg/L. These findings suggest that benzothiazole and benzoxazole selenones represent promising lead compounds for sustainable plant disease management. Full article

The impacts of land use on stormwater runoff quality and Best Management Practices to mitigate these impacts have been investigated since the 1970s, yet challenges remain in providing a modeling approach that concomitantly considers contributions from different land use types. In densely developed urban areas, a buildup/washoff approach is often applied, while in rural areas, some type of erosion modeling is employed, as the processes of detachment, entrainment, and transport are fundamentally different. This study presents a coupled modeling approach within PCSWMM, integrating exponential buildup/washoff for impervious surfaces with the Modified Universal Soil Loss Equation (MUSLE) for pervious areas, including construction sites, to characterize water quality in the large mixed urban–rural Sparrovale catchment in Geelong, Australia. The watershed includes an innovative cascading system of 12 online NbS wetlands along one of the main tributaries, Armstrong Creek, to manage runoff quantity and quality, as well as 16 offline NbS wetlands that are tributary to the online system. A total of 78 samples for Total Suspended Solids (TSS), Total Phosphorus (TP), and Total Nitrogen (TN) were collected from six monitoring sites along Armstrong Creek during wet- and dry-weather events between May and July 2024 for model validation. The data were supplemented with six other catchment stormwater quality datasets collected during earlier studies, which provided an understanding of water quality status for the broader Geelong region. Results showed that average nutrient concentrations across all the sites ranged from 0.44 to 2.66 mg/L for TP and 0.69 to 5.7 mg/L for TN, spanning from within to above the ecological threshold ranges for eutrophication risk (TP: 0.042 to 1 mg/L, TN: 0.3 to 1.5 mg/L). In the study catchment, upstream wetlands reduced pollutant levels; however, downstream wetlands that received runoff from agriculture, residential areas, and, importantly, construction sites, showed a substantial increase in sediment and nutrient concentration. Water quality modeling revealed washoff parameters primarily influenced concentrations from established urban neighborhoods, whereas erosion parameters substantially impacted total pollutant loads for the larger system, demonstrating the importance of integrated modeling for capturing pollutant dynamics in heterogeneous, urbanizing catchments. The study results emphasize the need for spatially targeted management strategies to improve stormwater runoff quality and also show the potential for cascading wetlands to be an important element of the Nature-based Solution (NbS) runoff management system. Full article

Diabetes is a developing global health concern that cannot be cured, necessitating frequent blood glucose monitoring and dietary management. Photoacoustic Spectroscopy (PAS) in the mid-infrared (MIR) region has recently emerged as a viable noninvasive blood glucose monitoring technique. However, MIR-PAS confronts significant challenges: (i) Water absorption, which reduces light penetration, and (ii) interference from other blood components. This paper systematically analyzes the background of photoacoustic signal generation and proposes a differential PAS (DPAS) in the MIR region for removing the background signals arising from water and other interfering components of blood, which improves the overall detection sensitivity. A detailed mathematical model with an explanation for choosing two suitable MIR quantum cascade lasers for this differential scheme is presented here. For single-wavelength PAS (SPAS), a detection sensitivity of $1.537$ µPa mg⁻¹ dL was obtained from the proposed model. Alternatively, $2.333$µPa mg⁻¹ dL detection sensitivity was found by implementing the DPAS scheme, which is about 1.5 times higher than SPAS. Moreover, DPAS facilitates an additional parameter, a differential phase shift between two laser responses, that has an effective correlation with the glucose concentration variation. Thus, MIR-based DPAS could be an effective way of monitoring blood glucose levels noninvasively in the near future. Full article

Background/Objectives: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage or with metastases. Detecting cancer at an early stage significantly increases the likelihood of a cure; therefore, research on new markers and a thorough understanding of tumor biology are essential. This study investigated the significance of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) as potential biomarkers in ccRCC. Methods: ARO, CTSS, and MMP-1 concentrations in plasma were determined using SPRi biosensors. Appropriate antibodies were used as biorecognition molecules in the biosensors. The samples analyzed came from 60 patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and from 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Results: A statistically significant increase (p < 0.00001) in the concentration of all proteins compared with the control samples was observed at the T3–T4 stage. The ARO concentration was already statistically significantly higher at the T1–T2 stage (p < 0.00001). The ROC curve for aromatase demonstrated high sensitivity and specificity for detecting ccRCC, with a cut-off point of 7.53 ng mL⁻¹. A moderate positive correlation was also found between the concentrations of the three tested substances in renal cancer, which may indicate potential interactions in the tumor’s pathogenesis. Conclusions: SPRI testing has been shown to be an alternative to standard methods for detecting potential ccRCC markers. The biosensors used in the study can simultaneously determine ARO, CTSS, and MMP-1. The results obtained suggest the potential importance of these proteins in the development of ccRCC, and our work proposes a new diagnostic technique that may aid in the diagnosis of ccRCC. Full article

Aspergillus fumigatus, a saprophytic fungus, causes aspergillosis, primarily affecting the immunocompromised. The efficacy of triazole antifungals is compromised by resistance that has developed both clinically and environmentally. Widespread agricultural use of similar triazole fungicides selects for resistant genotypes, leading to potential food contamination and compromising treatment. This study assessed the presence of azole-resistant A. fumigatus in minimally processed food items commonly consumed in Brazil. A total of 25 commercial samples, including black pepper, yerba mate, and green coffee beans, were collected from different regions. Forty-two A. fumigatus isolates were recovered and screened for susceptibility to agricultural and clinical triazoles by determining EC₅₀ values for tebuconazole (0.04–0.7 µg/mL), itraconazole (0.06–0.5 µg/mL), and voriconazole (0.07–0.15 µg/mL). Sequence analysis of the CYP51A gene revealed the presence of M172V mutation, none of which are associated with resistance. Microsatellite genotyping indicated high genotypic diversity and genetic relatedness among isolates from different food sources. Although no azole-resistant phenotypes were identified, the consistent recovery of A. fumigatus from products not directly exposed to azole fungicides highlights the need for continued surveillance. Agricultural environments remain critical hotspots for the emergence and dissemination of resistance, reinforcing the importance of integrated One Health strategies in antifungal resistance monitoring. Full article

Background/Objectives: Coronary artery disease (CAD) is highly prevalent in patients undergoing vascular surgery and is a major determinant of postoperative morbidity and mortality. Preoperative anemia is a well-recognized risk factor for adverse outcomes, including major adverse cardiac events (MACEs), but its independent impact in patients with CAD undergoing abdominal aortic aneurysm (AAA) repair remains unclear. Methods: We conducted a retrospective cohort study of 410 consecutive patients undergoing open AAA repair at a tertiary vascular center between 2023 and 2025. Preoperative anemia was defined as hemoglobin < 130 g/L and significant CAD as ≥70% luminal narrowing for non-left main disease or ≥50% for left main disease. The primary outcome was MACE (cardiovascular death, myocardial infarction, or stroke) during hospitalization. Baseline covariates included age, sex, diabetes mellitus (DM), chronic kidney disease (CKD), congestive heart failure (CHF), peripheral artery disease (PAD), and other relevant comorbidities. Multivariable logistic regression models were used to evaluate associations of anemia, CAD, and their interaction with MACE. Additionally, a composite risk group was created to examine MACE rates across mutually exclusive subgroups. Results: Among 410 patients, 314 (76.6%) had CAD and 116 (28.3%) had preoperative anemia. Overall, 67 patients (16.3%) experienced MACE. In the reduced model including only anemia and CAD, anemia remained a strong independent predictor of a MACE (OR 4.46, 95% CI 2.57–7.72, p < 0.001), and CAD was also independently associated (OR 2.20, 95% CI 1.00–4.72, p = 0.044). In the full multivariable model adjusting for DM, CHF, CKD, PAD, and age, anemia was the strongest predictor (OR 4.53, 95% CI 2.49–8.26, p < 0.001), while CAD showed a borderline association (OR 2.07, 95% CI 0.94–4.57, p = 0.071). Interaction analysis indicated no statistically significant modification in risk by the combination of anemia and CAD. The composite risk group variable was omitted due to collinearity with its components. Conclusions: Preoperative anemia, particularly in patients with CAD, is a significant and independent predictor of major adverse cardiac events following open AAA repair. These findings support the importance of early identification and correction of anemia before surgery to improve perioperative cardiac outcomes in this high-risk population. Full article

Background: Metabolic syndrome (MetS) is influenced by behavioral and genetic factors, yet evidence on eating behavior patterns and related genetic polymorphisms in Central Asian populations remains limited. Aim: The aim of this study was to assess eating behaviors among adults with and without MetS and evaluate their associations with clinical indicators and ADIPOQ rs266729 and MC4R rs17782313 variants. Methods: A cross-sectional study of 200 adults (115 non-MetS, 85 MetS) was conducted using Dutch Eating Behavior Questionnaire (DEBQ), standardized clinical measurements, and PCR-RFLP genotyping. Results: Participants with MetS were older than non-MetS adults (52 vs. 47 years; p = 0.004) and had substantially higher systolic blood pressure (126 vs. 114 mmHg; p < 0.001), diastolic blood pressure (83 vs. 74 mmHg; p < 0.001), and BMI (32.2 vs. 25.9 kg/m²; p < 0.001). Waist circumference, hip circumference, triglycerides, total cholesterol, and LDL were also significantly higher, while HDL was lower (1.13 ± 0.40 vs. 1.58 ± 1.50 mmol/L; p = 0.008). DEBQ restrained, emotional, and external eating scores showed no differences between groups (all p > 0.05). Eating behavior distribution was similar (p = 0.291). ADIPOQ genotypes (CC/CG/GG) did not differ by MetS status (p = 0.227), nor did MC4R variants (p = 0.679). Among MetS participants, clinical indicators did not vary across eating behavior categories, and no associations were observed between eating behavior and either polymorphism. Conclusions: Despite clear clinical and metabolic differences between MetS and non-MetS groups, neither eating behavior patterns nor ADIPOQ and MC4R variants were associated with metabolic measures among MetS group. Full article

This scoping review aims to synthesize peer-reviewed literature exploring quality of life (QoL) for individuals with age-related hearing loss (ARHL), age-related central auditory processing (ARCAP) deficits, and age-related cognitive decline. A growing body of research has identified ARHL as a risk factor for the development of dementia, highlighting the connection between the sensory and cognitive systems. As the aging population continues to grow, examining comorbid age-related hearing and cognitive decline is especially relevant. These conditions may have potential negative consequences on the daily functioning, social participation, mental health, and overall wellbeing of older adults. A systematic search of peer-reviewed literature was conducted across multiple databases, adhering to the PRISMA guidelines for scoping reviews. Studies that focused on the impact of ARHL, ARCAP deficits, and/or related cognitive deficits on QoL were included in the present review. Key data extracted included QoL measures categorized into the ICF framework, the effects of hearing loss intervention on QoL, and the impact of ARHL on QoL for aging individuals. This review summarizes the reported effects that ARHL, ARCAP, and/or cognitive decline have on older adults, and discusses the clinical and practical implications for managing clients with these conditions. In addition to preventative measures and deficit management, maintenance of life participation, social engagement, and overall wellbeing should be considered when caring for aging adults with hearing and/or cognitive impairment. Full article

Background/Objective: Current treatments for peripheral nerve injury (PNI) lack robust evidence to suggest complete recovery; hence, alternative therapeutics offer new opportunities to develop more effective protocols. Mushroom species and their related components are considered potential candidates for peripheral nerve repair, but their specific effects and underlying mechanisms are not fully understood. This systematic review presents the available evidence on the use of mushroom species for PNI therapy, including the bioactive components and mechanisms of action. Methodology: A comprehensive literature search in three databases (PubMed, Scopus, and Google Scholar) led to the synthesis of 11 records published between 2010 and 2024. Qualitative analysis revealed the neuroregenerative potential of four mushrooms: Amanita muscaria (n = 2), Hericium erinaceus (n = 5), Lignosus rhinocerotis (n = 3), and Flammulina velutipes (n = 1), with aqueous extracts as the most common type of ingredients used (n = 4) relative to specific components such as muscimol, polysaccharide, Erinacine S, and nerve-guided conduits (NGCs). Results: These mushroom-derived treatments enhanced the migration of Schwann cells mainly via the FGF-2 signalling and MAPK pathway. In vivo studies also revealed the ability of H. erinaceus, A. muscaria, and L. rhinocerotis to promote peripheral nerve repair and functional recovery, with evidence suggesting the role of neurotrophic factors, anti-apoptotic signalling, and pro-inflammatory substances. H. erinaceus was identified as the most promising for potential clinical applications, given the stronger evidence-based data and its relatively safer components compared to A. muscuria and other mushroom species. Conclusions: Despite presenting the potential use of mushrooms in managing PNIs, the existing approaches need to be subjected to clinical research to accelerate the development of future therapeutics and preventive measures for PNIs. Full article

Perfluorooctanoic acid (PFOA) is a persistent and bioaccumulative hazardous pollutant, presenting substantial threats to the environment and human health. The dual-mode, portable, sensitive, low-background, and cost-effective detection methods for PFOA were developed by integrating up-conversion fluorescent silicon quantum dot–molecularly imprinted polymer (MIPs) with a smartphone-based sensing system. The interaction between PFOA and MIPs resulted in a fluorescence quenching with a range of 2–20 µmol/L and a limit of detection (LOD) of 37.5 nmol/L for the low-background up-conversion fluorescence detection of PFOA, whereas the portable smartphone sensing platform enabled the detection of PFOA with a linear range of 0–5 µmol/L and a LOD of 73.9 nmol/L. Furthermore, the established methods were successfully applied to the detection of PFOA in environmental waters and food samples. This study provides the dual-mode, portable, novel, practical and low-background approaches for the detection of PFOA in the environment and food products. Full article